title: Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome.
abstract: OBJECTIVE
  A multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma.
  
  
  METHODS
  Patients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor.
  
  
  RESULTS
  Fifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33).
  
  
  CONCLUSIONS
  R-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.
authors.affiliation: Patrick G. Morris, Denise D. Correa, Joachim Yahalom, Anne S. Reiner, Kathy Panageas, Sasan Karimi, Richard Curry, Gaurav Shah, Lauren E. Abrey, Lisa M. DeAngelis, and Antonio Omuro, Memorial Sloan-Kettering Cancer Center; Rose K. Lai, Columbia University, New York, NY; Jeffrey J. Raizer and Sean Grimm, Northwestern University, Chicago, IL; David Schiff, University of Virginia, Charlottesville, VA; and Barbara Grant, University of Vermont, Burlington, VT.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.forename: Denise D
authors.initials: DD
authors.lastname: Correa
authors.forename: Joachim
authors.initials: J
authors.lastname: Yahalom
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Barbara
authors.initials: B
authors.lastname: Grant
authors.forename: Sean
authors.initials: S
authors.lastname: Grimm
authors.forename: Rose K
authors.initials: RK
authors.lastname: Lai
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Kathy
authors.initials: K
authors.lastname: Panageas
authors.forename: Sasan
authors.initials: S
authors.lastname: Karimi
authors.forename: Richard
authors.initials: R
authors.lastname: Curry
authors.forename: Gaurav
authors.initials: G
authors.lastname: Shah
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.forename: Lisa M
authors.initials: LM
authors.lastname: DeAngelis
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D013995:Time; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D011344:Procarbazine; D000069283:Rituximab; D014750:Vincristine; D008727:Methotrexate